Betulinic acid is 3β-hydroxy-lup-20(29)-ene-28-acid of formula 
It is known that betulinic acid is effective against the growth of melanoma cells (e.g. Pisha et al., Nature Medicine 1, 1995, 1046 ff) as well as against other cancer cells (e.g. Sunder et al., U.S. Pat. No. 6,048,847). In addition its amides are supposed to be suitable for use against HIV (e.g. Evers et al., J. Med. Chem. 39, 1996, 1056 ff; or Soler et al., J. Med. Chem. 39, 1996, 1069 ff). Consequently betulinic acid is in great demand.
Apart from being produced synthetically (e.g. L. Ruzicka et al., Helv. Chim. Acta 21, 1938, 1076 ff) betulinic acid may also be obtained from various plants, particularly trees, such as for example from the outer bark or cortex of Picramnia pentandra (e.g. Herz et al., Phytochemistry 11, 1972, 3061 ff), from the cortex of Arbutus menziesii (Robinson et al.,
Phytochemistry 9, 1970, 907 ff) and from the cortex of Ziziphus mauritiana (e.g. Pisha et al., Nature Medicine 1, 1995, 1046 ff).
It is difficult to isolate betulinic acid from these starting materials. By contrast it would appear more promising to obtain it from the cortex and/or bark of the plane tree (Platanus acerifolia). DE 197 13 768 proposes a process for obtaining betulinic acid, in which a powder obtained from plane bark is extracted with a medium polarity solvent such as for example dichloromethane, chloroform or diethyl ether.
However, this process is unsuitable for the industrial recovery of large amounts of betulinic acid, as very large volumes of the medium polarity solvent have to be used to extract the betulinic acid (7 litres of dichloromethane are used to 150 g of powdered plane tree bark).
Bruckner et al., J. Chem. Soc. 1948, 948-951 describe a process for obtaining betulinic acid from plane bark in which the ground bark is extracted with methanol, the extract obtained is evaporated down, and the concentrate is repeatedly recrystallised from methanol in the presence of charcoal. However, the betulinic acid thus obtained still contains a large number of impurities.
The aim of the present invention was therefore to provide an improved process for the large-scale recovery of highly pure, crystalline betulinic acid from plane bark and/or plane tree cortex which avoids the disadvantages of the known methods.